Wounds and uncontrolled bleeding or hemorrhage remains the leading cause of preventable death following trauma. It is thought that about ⅓ of these deaths occur later than 10 minutes after injury, suggesting that effective and timely treatment can be useful in reducing deaths from wounds and hemorrhage. Treatments to control bleeding include fluid resuscitation, hemostatic dressings, pressure devices and drugs.
For treatment, it can be necessary to discover the source of bleeding. The source is either visible (e.g., arterial bleeding in limb trauma etc.) or invisible (e.g., internal bleeding). It can also be necessary to evaluate the amount of blood loss and potential for organ damage (e.g., cerebral coma after intracranial bleeding). A common feature observed during hemorrhagic shock is the drop in mean arterial pressure. The arterial pressure in case of Stage I and II has moderate drop but in Stage III and IV, the drop is significant and rapid treatment is necessary to control the bleeding and bring the body under hemostasis.
Hemorrhagic shock is typically treated by volume replacement, either with full blood or crystalloids followed by infusion of hemostatic agents to restore hemostasis. Three factors for normal hemostasis are: vessel wall, platelets, and plasma proteins (e.g., coagulation factors). Primary hemostasis occurs in seconds, as a platelet plug is formed. There are four steps of primary hemostasis: platelet activation, adhesion, degranulation and aggregation. During secondary hemostasis, coagulation factors of internal and external cascade are activated and fibrin is formed from fibrinogen.
However, volume replacement therapy can cause blood to lose its ability to clot resulting in coagulopathy by altering the coagulation factors. Coagulopathy can be attributed to a combination of factors: (a) depletion and dilution of coagulation factors and platelets, (b) metabolic acidosis, and (c) hypothermia. Depletion and dilution of coagulation factors and platelets can be due to the transfusion of crystalloid solutions, the body's rapid consumption of factors and platelets as it tries hard to achieve hemostasis and intravascular coagulation. In addition, metabolic derangements and hypothermia have been focused on as two variables that play a major role in maintaining hemostasis following bleeding. It has been observed that temperature drop from 37° C. to 33° C. drastically reduced the ability of platelets to form clots. Small changes in pH also reduces the activity of various enzymes involved in the coagulation process For example, a pH decrease from 7.4 to 7.0 has been found to reduce the activity of enzyme that activates thrombin by 70%. The replacement of missing factor(s) such as platelet and plasma proteins is needed to treat this condition. In addition, restoration of complete hemostasis in the body can require the introduction of hemostatic agents.
Current in vitro models for testing wound healing and hemostatic efficacy of a dressing or agents rely primarily on experiments performed in static environments of test tubes. However, results obtained from these simplified experiments are not predictive of animal or human vascular injury. This is due to the fact that in vivo conditions are significantly different than the experimental conditions in vitro. They fail to reproduce both the injury characteristics (e.g., wound size, dilution, pH/temperature change) and the variety of physiological (e.g., blood flow, platelet adhesion) and biological (e.g., endothelial response, coagulation pathway) mechanisms involved in wound healing and stopping hemorrhage. This leads to critical deficits in the understanding of the interplay and relative importance of these mechanisms in wound healing and restoring hemostasis. Therefore, there remains a need in the art for a better system and methodology for studying wound healing and hemostasis.